The objectives of this research are to characterize in vitro plasma membrane-induced inhibition of cell growth, and to purify the plasma membrane component which is responsible for this inhibition. The membrane inhibiting effect will be characterized by adding isolated plasma membranes to cultures of sparse, actively growing 3T3 cells, a mouse fibroblast cell line. Effects of these membranes on mitogen (EGF) binding and internalization, and on subsequent growth rates will be determined. Studies on the membrane induced effect on hormone-receptor interactions, by removing the membranes or otherwise reversing the membrane induced effect will be made. Isolation of the growth inhibiting membrane factor will follow membrane protein isolation procedures. Initial procedures will involve differential solubilization of protein species, protein separation by isoelectric focusing and differential protein incorporation into liposomes. Reconstitution studies will allow the investigator to characterize the membrane related requirements of the growth inhibiting parameter. The information obtained from these investigations will help to clarify the membrane related aspect of density dependent inhibition of growth, to the level of identifying the membrane component involved. Comparisons between normal and transformed systems of this effect will be made and may lead to a better understanding of the alterations in membrane structure and function that contribute to cell transformation.